Various glycoproteins (GP) are present on the surface of a platelet, and involved in the expression of platelet function. As such platelet glycoproteins, GPIb, GPIIb, GPIIIa, GPIIIb, GPIV, GPIX and the like are known. Of these, GPIb functions as a receptor of the von Willebrand factor (vWF). GPIb is a heterodimer having a molecular weight of 160,000, wherein α chain and β chain are disulfide-bonded.
Recently, platelet substitutes are known, which have a functional macromolecule (e.g., GPIb, a recombinant 45 kDa hydrophilic part of α chain (rGPIbα), GPIIb/IIIa and the like) bound with the surface of a certain micro particle. Of these, those having rGPIbα are expected to function as a platelet substitute since they show an adhesive action resulting from the interaction between rGPIbα and the vWF. On the other hand, those having GPIIb/IIIa are expected to function as a platelet substitute since they show a coagulating action resulting from the interaction between GPIIb/IIIa and fibrinogen and/or vWF.
In addition, as micro particles bound these functional macromolecules, lipid membrane such as vesicle and the like, human albumin or polymer thereof, human red blood cell and the like are known, and patent reference 1 describes rGPIbα-bound vesicle.
Also, there are some known to induce hematological coagulation by aiding the platelet activity remaining in the patient blood, rather than to function as a platelet substitute since it has a functional macromolecule on the platelet. For example, one that induces platelet aggregation by interacting with GPIIb/IIIa on the platelet is known. To be specific, a conjugate of a vesicle and a peptide containing dodecapeptide (H12) contained in the GPIIb/IIIa recognition site of fibrinogen bound thereto is described in non-patent reference 1.
Patent references 2 and 3 describe conjugates having a linker inserted between GPIb or dodecapeptide, and vesicle, and teach that the conjugates can be used as drug delivery materials for physiologically or pharmacologically effective drugs by accumulating the conjugates on the injury site of blood vessels.
In addition, non-patent reference 2 describes a vesicle carrying adenosine diphosphate (ADP). ADP is a substance known to induce platelet aggregation or thrombus formation. This vesicle releases ADP by laser irradiation and induces platelet aggregation.
However, none of the aforementioned references disclose a drug delivery material that spontaneously releases a drug only at a desired site to achieve a pharmacological effect.
While patent references 2 and 3 describe use of the conjugates described therein as drug delivery materials, they do not describe specific embodiments thereof. Furthermore, while non-patent reference 2 describes a vesicle carrying ADP, the vesicle requires an external means of laser irradiation for releasing ADP.
patent reference 1: JP-A-9-208599
patent reference 2: WO01/64743
patent reference 3: WO2004/069862
non-patent reference 1: T. Nishiya et al., Thromb Haemost, 91, 1158-67 (2004)
non-patent reference 2: B. Khoobehi et at., Lasers Surg Med., 12(6), 609-14, 1992